Effects of exposure to amphetamine derivatives on passive avoidance performance and the central levels of monoamines and their metabolites in mice: correlations between behavior and neurochemistry.
Effects of exposure to amphetamine derivatives on passive avoidance performance and the central levels of monoamines and their metabolites in mice: correlations between behavior and neurochemistry.
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DOI：
10.1007/s00213-011-2504-0
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发表时间：
2012-04-01
影响因子：
3.4
通讯作者：
Fantegrossi, William Edward
中科院分区：
文献类型：
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作者：
Murnane, Kevin Sean;Perrine, Shane Alan;Fantegrossi, William Edward
依据：大量证据表明安非他明衍生物可消耗脑单胺能神经递质。然而，安非他明引起的神经化学物质消耗的行为和认知后果还没有得到很好的建立。结论：在这项研究中，小鼠暴露于已知消耗单胺神经递质多巴胺和5-羟色胺的3，4-亚甲二氧基甲基安非他明（MDMA），甲基安非他明（METH）或对氯安非他明（PCA）的给药方案，并评估这些给药方案对学习和记忆的影响。在相同的动物中，我们通过被动回避（PA）行为确定了学习和记忆的缺陷，并通过离体高压液相色谱法确定了纹状体、额叶皮质、扣带回、海马和杏仁核中单胺神经递质及其初级代谢物的组织含量的变化。暴露于METH和PCA损害PA性能，并导致多巴胺，血清素及其代谢产物在几个大脑区域的显着消耗。多元线性回归分析表明，多巴胺在前纹状体的组织浓度是最强的预测PA性能，与扣带回中的5-羟色胺代谢物5-羟基吲哚乙酸的组织浓度的额外的显着贡献。与甲基苯丙胺和PCA的影响相比，暴露于MDMA没有耗尽前纹状体多巴胺水平或扣带回水平的5-hydroxyindoleacetate acid.CONCLUSIONS：这些研究表明，某些安非他明损害PA的性能在小鼠和这些损害可能是由于特定的神经化学物质消耗。
RATIONALE: Considerable evidence indicates that amphetamine derivatives can deplete brain monoaminergic neurotransmitters. However, the behavioral and cognitive consequences of neurochemical depletions induced by amphetamines are not well established.OBJECTIVES: In this study, mice were exposed to dosing regimens of 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine (METH), or parachloroamphetamine (PCA) known to deplete the monoamine neurotransmitters dopamine and serotonin, and the effects of these dosing regimens on learning and memory were assessed.METHODS: In the same animals, we determined deficits in learning and memory via passive avoidance (PA) behavior and changes in tissue content of monoamine neurotransmitters and their primary metabolites in the striatum, frontal cortex, cingulate, hippocampus, and amygdala via ex vivo high-pressure liquid chromatography.RESULTS: Exposure to METH and PCA impaired PA performance and resulted in significant depletions of dopamine, serotonin, and their metabolites in several brain regions. Multiple linear regression analysis revealed that the tissue concentration of dopamine in the anterior striatum was the strongest predictor of PA performance, with an additional significant contribution by the tissue concentration of the serotonin metabolite 5-hydroxyindoleacetic acid in the cingulate. In contrast to the effects of METH and PCA, exposure to MDMA did not deplete anterior striatal dopamine levels or cingulate levels of 5-hydroxyindoleacetic acid, and it did not impair PA performance.CONCLUSIONS: These studies demonstrate that certain amphetamines impair PA performance in mice and that these impairments may be attributable to specific neurochemical depletions.